Enhancing Prolonged Exposure With Cannabidiol to Treat Posttraumatic Stress Disorder

Enhancing Prolonged Exposure With Cannabidiol to Treat Posttraumatic Stress Disorder: A Pilot Study

The primary goal of this pilot project is to demonstrate the safety and feasibility of using Cannabidiol (CBD) in combination with standard of care prolonged exposure (PE) psychotherapy to reduce PTSD symptoms.

Study Overview

• Status: Completed
• Conditions: Stress Disorders, Post-Traumatic; Posttraumatic Stress Disorder
• Intervention / Treatment: Drug: Cannabidiol (CBD) oral solution; Behavioral: Massed Prolonged Exposure (mPE); Drug: Placebo

Detailed Description

This study is an early Phase II double-blind, pilot randomized controlled clinical trial. The study team will use a permuted block randomization design stratified by a Posttraumatic Stress Disorder (PTSD) severity median score on the PTSD Checklist (PCL-5) derived from a recently completed STRONG STAR repository. Participants will be up to 24 individuals with PTSD to investigate the safety, feasibility, and PTSD symptom change associated with CBD 250mg taken twice a day for 18 days (n=up to 12) vs. placebo (n=up to12) in combination with a standard of care, 10-sessions massed PE psychotherapy administered over 2 weeks. Aims 2 and 3 will evaluate biochemical and physiological outcomes associated with the brain endocannabinoid (eCB) and PTSD that may be affected by CBD. Permuted block randomization is advantageous in small clinical trials to ensure equal allocation of participants in each condition. Participant randomization will be subdivided into randomized blocks of four, two patients in each block will be assigned to CBD and two will be assigned to placebo.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio - STRONG STAR Northwest Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Individuals between the age of 18 to 65 years old at time of screening.
2. Able to write, read, and speak English
3. PTSD diagnosis as assessed by Clinician-Administered Posttraumatic Stress Scale (CAPS-5)
4. Stable medication regimen for at least four weeks prior to the onset of study participation.

Exclusion Criteria:

1. History of opiate, cocaine, methamphetamine, benzodiazepine, or cannabis abuse as determined by the National Institute of Drug Abuse Quick Screen (NIDA-Q).
2. Currently using opiates, cocaine, methamphetamines, benzodiazepines, or cannabis as evidenced by a positive urine drug screen prior to enrollment.
3. Currently pregnant as determined by a positive urine pregnancy test prior to enrollment.
4. Current clinically significant alcohol abuse in the past two weeks on the Quick Drinking Screen (QDS).
5. Currently breastfeeding.
6. Ongoing illness or physical health problem(s) that may be exacerbated by CBD (e.g., history of liver problems)
7. History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to cannabinoids.
8. Concomitant medications with possible CBD-drug interactions
9. Alanine transaminase (ALT) or Aspartate transaminase (AST) enzyme levels 3x normal limits.
10. Concurrent engagement in trauma-related psychotherapy for PTSD.
11. Current or past DSM-5 diagnosis of psychotic disorder or bipolar disorder as determined on the Mini International Neuropsychiatric Interview (MINI 7.0).
12. Suicide attempt in the last year and/or suicide risk requiring immediate intervention or requiring a higher level of care than can be provided by the study treatment as determined by the Self-Injurious Thoughts and Behaviors Interview (SIT-BI).
13. Allergy to sesame seed oil.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cannabidiol (CBD); Epidiolex oral solution 500mg (5ml) per day	Drug: Cannabidiol (CBD) oral solution; An oral strawberry flavored liquid, taken as a 2.5ml (250mg) dose twice a day; Other Names: Epidiolex; Behavioral: Massed Prolonged Exposure (mPE); mPE, delivered daily Monday through Friday over two weeks, utilizes exposure-based interventions to target psychological mechanisms (i.e., experiential and behavioral avoidance; maladaptive cognitive changes) that are thought to maintain trauma-related symptoms.; Other Names: Behavioral Therapy
Placebo Comparator: Placebo; Placebo oral solution 5ml per day	Behavioral: Massed Prolonged Exposure (mPE); mPE, delivered daily Monday through Friday over two weeks, utilizes exposure-based interventions to target psychological mechanisms (i.e., experiential and behavioral avoidance; maladaptive cognitive changes) that are thought to maintain trauma-related symptoms.; Other Names: Behavioral Therapy; Drug: Placebo; An inert strawberry flavored oral solution, taken as a 2.5ml dose twice a day; Other Names: Placebo oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician Administered PTSD Scale (CAPS-5)	The CAPS-5 is structured interview that assesses the Diagnostic and Statistical Manual of Mental Disorders v5 (DSM-5) criteria for PTSD. Each item is rated on a severity scale ranging from 0 (Absent) to 4 (Extreme/incapacitating) and combines information about frequency and intensity for each of the 20 symptoms.Subscale scores are calculated by summing severity scores for items in the following PTSD symptom clusters: re-experiencing, avoidance, negative alterations in cognitions and mood, and hyperarousal. Scores ≥ 25 indicate a probable diagnosis of PTSD. Scores range from 0 to 80. Change in score will be reported.	Baseline and at about 45 days (1 month follow-up visit)
Posttraumatic Stress Disorder Checklist (PCL-5)	The PCL-5 is a 20-item self-report measure update of the PCL designed to assess PTSD symptoms as defined by the DSM-5. The PCL-5 evaluates how much participants have been bothered by PTSD symptoms in the past week (for all assessments during treatment) or the past two weeks (all other assessment time points) as a result of a specific life event. Each item of the PCL-5 is scored on a five-point scale ranging from 0 "not at all") to 4 ("extremely). Scores range from 0 to 80 with a higher score indicating that subjects have been bothered more by PTSD symptoms. Change in score will be reported.	Baseline and at about 45 days (1 month follow-up visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Health Questionnaire-9 (PHQ-9)	It consists of 9 items that assess both affective and somatic symptoms related to depression and depressive disorders; these 9 items correspond to the diagnostic criteria for Diagnostic Statistical Manual of Mental Disorders - Major Depressive Disorder (DSM MDD). Respondents rate the frequency with which they have been bothered by depressive symptoms within the past two weeks on a scale ranging from 0 ("not at all") to 3 ("nearly every day"). Scores on all items are summed to obtain a total severity score between 0 and 27. Scores reflect no significant depressive symptoms (0-4), mild depressive symptoms (5-9), moderate depressive symptoms (10-14), moderately severe depressive symptoms (15-19), and severe depressive symptoms (>19). Change in score is reported.	Baseline and at about 45 Days (1 month follow-up visit)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Casey Straud, PsyD, University of Texas Health Science Center San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2022
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: November 12, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Anticonvulsants; Pharmaceutical Solutions; Cannabidiol
• Other Study ID Numbers: HSC20210711H; UL1TR002645 (U.S. NIH Grant/Contract); KL2TR002646 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

A STRONG STAR Institutional Review board (IRB) approved Repository to enable the STRONG STAR Consortium to store specimens and data for future use. Study databases are established and maintained by the STRONG STAR Data and Statistics Services. All Repository data will be identified with a different code number that can be cross linked to the original study code only through records maintained by the STRONG STAR Data and Statistics Services. At the conclusion of this study, participants who signed the consent to have their data placed in the STRONG STAR Repository will be maintained under the UT Health San Antonio IRB-approved Repository protocol. For participants who decline participation in the STRONG STAR Repository, their data will be de-identified, and the data maintained in the Repository without identifiers.

Summary results will also be shared on ClincalTrials.gov.

• IPD Sharing Time Frame: After study enrollment is closed and data analysis is complete. Data will be stored in the repository and accessible as long as the IRB approval for this data base remains current.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes